Cardiovascular diseases rank as America's primary killer, claiming the lives of over 41% of more than 2.4 million Americans who die each year. One of the main reasons for this high number of lives lost is the severe lack of an effective imaging technique for early detection and localization of an abnormality upon anomaly detected on the electrocardiogram (ECG). It has been established that the mechanical and electrical properties of the myocardium change dramatically as a result of a myocardial ischemia; both at its onset and after survival. Despite these findings, no imaging technique currently exists that is routinely used in the clinic and can provide reliable, non-invasive, quantitative mapping of the regional, mechanical and electrical function of the myocardium. The underlying hypothesis of the renewal study is that elastographic techniques can detect and diagnose both the mechanical and electrical properties of the myocardium, both in its normal and disease, i.e., ischemic and infarcted, states. We propose to use this multi-dimensional, angle-independent elastographic technique at variable heart rates for early detection of disease based on its altered mechanical and electrical properties of the myocardium, which can now be obtained simultaneously. Most importantly, we propose to carefully assess its potential in the clinic for early detection and localization of ischemia by developing an optimized system that can be easily be integrated with standard echocardiography. To this purpose, a multidisciplinary team of investigators from Columbia University and Johns Hopkins University has been assembled. In order to test the aforementioned hypothesis, we propose the following specific aims: 1) determine capability of estimation of both electrical and mechanical properties of normal and ischemic/infarcted myocardium using a bi-domain simulation model; 2) develop upgraded system and test performance on tissue-mimicking phantoms undergoing 3D deformation and propagating waves; 3) validate and combine estimation of electrical and mechanical properties in the canine myocardium for early detection of ischemia and infarction; and 4) optimize and validate localization of ischemia or arrhythmia in humans against angiography and electroanatomic mapping, respectively. Should the results of this study indicate high reliability of the elastographic findings for detection of early ischemic onset, this novel imaging system could be readily tested in a clinical setting as part of a standard protocol for early ischemia and infarction detection and its subsequent timely treatment.